No benefit in adding hypertonic saline to Pulmozyme for CF: Study
Combined CF treatment not found to improve patients' lung function
For people with cystic fibrosis (CF) taking Pulmozyme (dornase alfa), adding treatment with hypertonic saline — or HS for short — did not significantly improve lung function or reduce the risk of exacerbations compared with the approved therapy alone, a new study indicates.
The findings showed that CF patients with more severe disease generally were more likely to have been given the combined treatment.
But after accounting for underlying differences due to disease severity, “the difference in lung function and incidence rate of exacerbations between [CF patients carrying the F508del mutation] on HS and [Pulmozyme] and those on [Pulmozyme] only was not significantly different from zero for up to 5 years of HS administration,” the researchers wrote.
According to the team, “there is uncertainty whether HS has a treatment effect,” with the researchers noting “we did not detect a significant effect of HS on the outcomes of interest over [Pulmozyme] treatment alone.”
The study, “Effect of Hypertonic Saline on Lung Function as Add-On Treatment in People with Cystic Fibrosis Receiving Dornase-alfa: A Cystic Fibrosis Foundation Patient Registry Analysis,” was published in the journal Chest. The work was funded by the Cystic Fibrosis Foundation.
Comparing CF treatment options in patients with F508del mutation
CF is characterized by the production of unusually thick, sticky mucus, which builds up in the lungs and other organs and causes most disease symptoms.
Pulmozyme and hypertonic saline are both inhaled agents that work as mucolytics — medications that help to break up and thin mucus, so it’s easier to clear from the airways. Both of these therapies are commonly used, alone or in combination. However, there hasn’t been much investigation into whether combining these treatments yields better results than one therapy alone.
Now, a team of researchers from the University of Missouri School of Medicine turned to the CF Foundation’s patient registry to learn more.
The researchers identified data on 1,241 people with CF who started on mucolytic treatment between 2006 and 2014. This time period was before the widespread availability of CFTR modulators, a recently developed class of therapy for patients with specific CF-causing mutations, the team noted.
Among the patients, 619 were treated with Pulmozyme alone, while the other 622 were given both Pulmozyme and hypertonic saline. All of these patients carried two copies of the most common CF-causing mutation, called F508del.
Before starting treatment, the CF patients given both Pulmozyme and hypertonic saline had significantly worse scores on measures of lung function compared with those given Pulmozyme only. Individuals given the combined therapy also had higher rates of serious exacerbations, or episodes when lung function suddenly worsens, typically due to an infection.
Over the course of five years of follow-up, lung function scores were consistently worse, and exacerbations consistently more common, among patients on the combined therapy. Overall, these findings suggest that patients who have more severe disease are generally more likely to be given combined treatment, the researchers said.
Researchers say any potential benefits of combo would be small
Next, the scientists used statistical models to account for the underlying difference in disease severity between the two groups. The results showed no statistically significant difference, in terms of the effect on lung function measures or exacerbation rates, for patients given combined therapy compared with Pulmozyme only.
Overall, the researchers concluded, there was no significant effect on the targeted patient outcomes with HS as an add-on therapy versus treatment with just Pulmozyme. They added that, based on the available data, even if a statistically significant effect could be detected, it would be relatively small — less than 4% on standard measure of lung function.
The team stressed that this finding represents an average, noting that the way any one person responds to treatment will be unique, so it’s still possible some patients may derive benefit from combined treatment.
This study also was limited to patients with a specific set of mutations who had detailed follow-up data available in the registry, the researchers noted. Thus, these results may not be generalizable to the broader CF community.